Baby Heart Transplants Fan Ethical Debate Over Dead-Donor Rule

MedPageToday ^ | 08.13.08 | John Gever

[Coleus]

Three heart transplants were successfully performed with infant donors whose hearts had stopped beating, according to researchers here, but some ethicists question whether moral boundaries were crossed. The report in the Aug. 14 issue of the New England Journal of Medicine reopened a long-simmering debate that boils down to the question of how to define death of a potential donor before organ harvesting may proceed. The three recipients, mean age 2.2 months, have survived at least 3.5 years with only one having a rejection episode during the first six months after surgery, reported Mark M. Boucek, M.D., and colleagues of the University of Colorado.

Echocardiography confirmed that mean heart function -- measured by left ventricular shortening fraction during systole and end-diastolic volume -- in the recipients did not differ significantly from that in 17 other infant transplant cases involving donors who met conventional brain-death criteria. The researchers said the results mean that more heart donations could be made available than is now typically the case, reducing waiting times and deaths among prospective transplant recipients.

"Many children die in children's hospitals each day after withdrawal of futile care," they wrote. Jeffrey M. Drazen, M.D., the NEJM's editor-in-chief, and two other NEJM editors pointed out that "although 400 pediatric cardiac transplantations are performed successfully each year (100 in infants under the age of one year), as many as 50 infants yearly are placed on the waiting list but die while waiting. Infants have 10 times the risk adults have of dying while waiting for an organ." Some medical ethicists and physicians, however, said the Denver transplant center may have declared the infant donors dead prematurely.

Currently, policy in the United States requires that donors must have been declared unequivocally dead for organ harvest to proceed, called the "dead-donor rule." Interpretations of the rule vary among institutions. Most transplants of hearts, whole livers, and both lungs are performed when donors meet brain-death criteria. But many facilities permit donations when donors are declared dead according to stoppage of heart rhythm.

Recent experience in adults has allayed concerns that cardiac death leaves organs too damaged to be transplanted safely. Dr. Boucek (now at Joe DiMaggio Children's Hospital in Hollywood, Fla.) and colleagues noted that kidney, liver, and lung transplants have become increasingly common following donor death from cardiocirculatory causes. They also said that pediatric heart transplants have been successfully completed with donors who died from sudden infant death syndrome and other prolonged ischemic injuries. But except for Dr. Christiaan Barnard's first case in 1967, no heart transplants had previously been performed following a donor's cardiocirculatory death.

Under a clinical trial protocol, they identified three newborns (mean age 3.7 days) with severe neurological damage as potential organ donors. The infants had terminal prognoses and were maintained on ventilator support but were not brain-dead. After obtaining consent from the prospective donors' parents, life support was withdrawn. With a death definition based on heart stoppage, death was declared in a mean of 18.3 minutes (range 11.5 to 27.5).

The Institute of Medicine has recommended defining cardiac death as a five-minute absence of heartbeats after withdrawal of ventilator support and other life-sustaining therapy, although some institutions have set the required interval to as little as two minutes. Dr. Boucek and colleagues waited three minutes before proceeding with organ harvest in their first case, but they shortened the interval to 75 seconds for the other two procedures on the recommendation of the hospital's ethics committee.

"This recommendation was based on the longest reported period before autoresuscitation of a child or adult, 60 seconds," Dr. Boucek and colleagues wrote. In one of three commentaries on the report also appearing in the NEJM, James L. Bernat, M.D., of Dartmouth Medical School in Hanover, N.H., criticized the 75-second interval as pushing the standard too far. "What minimum duration of asystole ensures that autoresuscitation will not occur is an empirical question that can be answered conclusively only after observing many hundreds of patients," Dr. Bernat wrote. He said restarting the heart successfully in the recipient could suggest its stoppage in the donor was not irreversible.

Dr. Bernat called on leaders of the relevant medical communities to draft practice guidelines for organ donation after cardiocirculatory death. "I predict that when prudent boundaries are created, they will exclude ... death determinations at 75 seconds of asystole," he said.

In another NEJM commentary, Robert Veatch, Ph.D., a biomedical ethicist at Georgetown University in Washington, opposed definitions of death that hinge on the impossibility of autoresuscitation. "Anyone who had had a cardiac arrest lasting beyond the time at which autoresuscitation was possible would be legally deceased, even if the heart had been successfully restarted through external stimulation," he argued.

The third commentary, by two other medical ethicists, countered that the dead-donor rule should be reconsidered. Robert D. Truog, M.D., of Children's Hospital Boston, and Franklin G. Miller, Ph.D., of the National Institutes of Health, contended that death definitions based on brain function were also flawed. "There have been persistent questions about whether patients with massive brain injury, apnea, and loss of brain-stem reflexes are really dead," they said.

Drs. Truog and Miller suggested replacing the dead-donor rule with a system that would allow some donations of hearts and other vital organs prior to a declaration of death, subject to clear criteria including informed consent. "Whether death occurs as a result of ventilator withdrawal or organ procurement, the ethically relevant precondition is valid consent by the patient or surrogate," they wrote. "With such consent, there is no harm or wrong done in retrieving vital organs before death." In an editorial, Dr. Drazen acknowledged the criticisms of the Denver transplant protocol and said the journal was publishing the paper "to foster discussion of donation after cardiocirculatory death in general and its application to infant heart transplantation in particular."

But they also appeared to side with Dr. Boucek and colleagues. "As a result of their investigational protocol, three babies are now alive; had the procedures not been performed, it is virtually certain that all six babies would be dead," Dr. Drazen and colleagues wrote. Dr. Boucek and colleagues said they had not undertaken their protocol lightly. "Before the trial was begun, an extensive period of education, discussion, and preparation was undertaken within our hospital and in programs already using donors who died from cardiocirculatory causes," they wrote. "After each transplantation involving these donors, there was extensive institutional debriefing and review by the ethics committee and the data and safety monitoring board."

The researchers said the availability of such donors should expand the pool of transplantable hearts. They added, however, that additional changes to the nationwide system for managing scarce donor organs would be needed to take full advantage. "This study was performed in the context of a large pediatric transplant program, yet most potential donors who underwent withdrawal from life support could not be considered, because there was no compatible local recipient," they said. Sharing of organs from patients dying of cardiocirculatory causes may need to cover a wider geographic area for it to make a national impact on waiting times, they said.

[LukeL]

Didn’t really read the article but I have heard since a infant has a weaker immune system the donor graft often takes and there are very few complications in many cases.